Safety evaluation in chickens of candidate human vaccines against potential pandemic strains of influenza.

Abstract Two candidate formalin-inactivated vaccines, made from high-growth reassortant viruses with the HA and NA genes from avian viruses in a background of genes derived from A/Puerto Rico/8/34 (PR8), were prepared against H5N1 and H9N2 subtypes (designated as H5N1/PR8 and H9N2/PR8, respectively). These viruses bear the genotypes, antigenicity, and attenuation in mouse models that are desirable in candidate vaccines. The pathogenicity of the newly generated avian-human reassortant vaccine viruses was also evaluated in chickens. Neither H5N1/PR8 nor H9N2/PR8 were highly pathogenic for chickens. No clinical signs, gross legions, or histological lesions were observed in chickens that were administered H5N1/PR8 either intranasally (i.n.) or intravenously (i.v.), and virus was not detected in oropharyngeal or cloacal swabs. When H9N2/PR8 was administered i.n., no clinical signs, gross lesions, or histological lesions were observed and no virus was detected in cloacal swabs. However, virus was isolated at lo...